Iron overload in myelodysplastic syndromes (MDS).

Iron overload in myelodysplastic syndromes (MDS). Int J Hematol. 2017 Nov 25;: Authors: Gattermann N Abstract Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with M...
Source: International Journal of Hematology - Category: Hematology Authors: Tags: Int J Hematol Source Type: research

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CONCLUSIONS: We found no evidence for a difference between participants receiving ATRA in addition to chemotherapy or chemotherapy only for the outcome OS. Regarding DFS, CRR and on-study mortality, there is probably no evidence for a difference between treatment groups. Currently, it seems the risk of adverse events are comparable to chemotherapy only.As quality of life has not been evaluated in any of the included trials, further research is needed to clarify the effect of ATRA on quality of life. PMID: 30080246 [PubMed - as supplied by publisher]
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
;ger U, Horny HP, Hermine O Abstract Pathologic erythropoiesis with consecutive anemia is a leading cause of symptomatic morbidity in internal medicine. The etiologies of anemia are complex and include reactive as well as neoplastic conditions. Clonal expansion of erythroid cells in the bone marrow may result in peripheral erythrocytosis and polycythemia but can also result in anemia when clonal cells are dysplastic and have a maturation arrest that leads to apoptosis and hinders migration, a constellation typically seen in the myelodysplastic syndromes. Rarely, clonal expansion of immature erythroid blasts result...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Purpose of review Sotatercept and luspatercept are recombinant soluble activin type-II receptor-IgG-Fc fusion proteins that are tested in clinical trials for the treatment of various types of anemias, including renal anemia. The mechanism of the action of the novel drugs is incompletely understood, but it seems to be based on the inactivation of soluble proteins of the transforming growth factor-ß (TGFß) family. This review considers pros and cons of the clinical use of the drugs in reference to the current therapy with recombinant erythropoiesis-stimulating agents (ESAs). Recent findings One or more activ...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research
Publication date: Available online 30 July 2018Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Chetasi Talati, David Sallman, Alan F. ListAbstractMyelodysplastic syndrome (MDS) with deletion 5q (del(5q)) is a distinct clinical and pathological disease subset that is exquisitely sensitive to lenalidomide for the treatment of red blood cell transfusion-dependent anemia. Lenalidomide resistance, including primary resistance occurs via clonal evolution which is frequently attributable to the presence of somatic mutations in in the DNA-binding domain of the TP53 gene. Treatment options after development of resistance t...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Myelodysplastic syndromes (MDS) are known to occur as an insufficiency of the bone marrow to produce a satisfactory amount of mature and functioning blood cells, resulting in cytopenia, especially in anemia in most cases, and dysplasia. MDS del(5q) is a subtype presenting with a deletion in the long arm of chromosome 5, which predominantly occurs in women and clinically presents with prominent anemia, dysmegakaryopoesis, often thrombocytosis and low blast counts in the bone marrow. As transformation rates into acute myeloid leukemia (AML) are relatively low and patients tend to suffer from mild symptoms compared to other s...
Source: Leukemia Research - Category: Hematology Authors: Source Type: research
Authors: Shallis RM, Chokr N, Stahl M, Pine AB, Zeidan AM Abstract INTRODUCTION: Myelodysplastic syndromes (MDS) encompass a heterogenous collection of clonal hematopoietic stem cell disorders defined by dysregulated hematopoiesis, peripheral cytopenias, and a risk of leukemic progression. Increasing data support the role of innate and adaptive immune pathways in the pathogenesis and disease course of MDS. The role of immunosuppressive therapy has an established role in the treatment of other hematologic diseases such as aplastic anemia whose pathogenesis is postulated to reflect that of MDS with regards to many as...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
Myelodysplastic syndrome (MDS) is rare in the pediatric age group and it may be associated with inheritable bone marrow failure (BMF) such as Fanconi anemia (FA). FA is a rare multi-system genetic disorder, ch...
Source: Molecular Cytogenetics - Category: Molecular Biology Authors: Tags: Case Report Source Type: research
We present a 2-year-old boy with splenomegaly, leukocytosis, thrombocytopenia, anemia, and excess myeloblasts with easily seen Auer rods, and marked dysgranulopoiesis and dyserythropoiesis. Conventional cytogenetic analysis showed a sole abnormality of t(3;5)(q25;q35). Microarray analysis showed a terminal 21 Mb region of copy-neutral loss of heterozygosity on 19q. Disease-related somatic NRAS mutation was detected. This case represents an unusual JMML with Auer rods and marked myelodysplasia. These unusual histopathologic features may be related to the t(3;5)(q25;q35). A t(3;5) with variable breakpoints has been reported ...
Source: Pathology Research and Practice - Category: Pathology Source Type: research
We report a case of delayed diagnosis of SDS in a family with another child with aplastic anemia, and review reported cases of SDS in Asia. This highlights the gap in identifying inherited bone marrow failure syndromes in adults with hematologic malignancies.
Source: Leukemia Research Reports - Category: Hematology Source Type: research
Publication date: August 2018Source: Hematology/Oncology Clinics of North America, Volume 32, Issue 4Author(s): Sharon A. Savage, Michael F. Walsh
Source: Hematology Oncology Clinics of North America - Category: Hematology Source Type: research
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